The proposed research seeks to learn more about hemostatic and fibrinolytic mechanisms through these approaches: 1) Observations on patients with congenital hemorrhagic diseases. In the hemophiliacs we have had a particular interest in frequent evidence of liver dysfunction and its relationship to treatment with factor concentrates. Liver biopsies have been done in about 20 individuals with abnormal liver function tests. Pathology has varied from chronic persistent hepatitis to chronic active hepatitis and cirrhosis. Special studies in Fletcher factor deficiency and Factor VII deficiency are underway. 2) Observations on patients with acquired hemorrhagic orthrombotic disease. A group of patients with acquired anti VIII are being studied. Also an investigation of another group of patients with different inhibitors (not anti-VIII) is being prepared for publication. 3) Study of the phologenetic development of coagulation mechanisms. The blood from many different animals from different vertebrate classes has been studied. Publications include studies on opossum, elephants, porpoise, monkeys, bats, hedgehogs, goats, echidna, elasmobranchs and turkeys. Studies are completed and being prepared for publications on pigs, dogs, rats and cats. An investigation of blood clotting in Amphibia is underway and will be completed in warmer weather when more animals can be shipped to our laboratory.